This Career Development Award will prepare the candidate, Carole D. Mitnick, Sc.D., for a career as an independent investigator in chronic, infectious disease epidemiology. The principal investigator (PI) completed a doctorate in population and international health at the Harvard School of Public Health and is currently an instructor in the Department of Social Medicine at Harvard Medical School. She proposes a three-year program that will comprise limited, specialized training in epidemiologic methods and an intensive, mentored research experience under the guidance of James Robins, M.D., a renowned epidemiologist; Garrett Fitzmaurice, Sc.D., a leader in longitudinal data analysis; and Paul Farmer, M.D., Ph.D., a preeminent infectious disease physician and anthropologist, and an architect of the multidrug-resistant tuberculosis (MDR-TB) treatment program in Peru where Dr. Mitnick's research is based. Using marginal structural models, the PI will estimate the relative effect of therapeutic and adjunctive alternatives for MDRTB on death and bacteriologic failure at or before the end of therapy. She has chosen this cutting-edge method, which was developed by Professor Robins, because it is well suited to the conditions surrounding this question. In order to draw causal inference from the observational, retrospective study of nearly 3,700 MDR-TB treatments in Peru, appropriate adjustment must be made for time-varying confounders, which are affected by prior treatment. Using inverse probability weighting, marginal structural models permit the estimation of the effect of the intervention, while adjusting appropriately for these covariates. This project will contribute substantially to the global evidence base for decision-making about the.treatment of MDR-TB, a Class C priority pathogen, in resource-poor settings. The Department of Social Medicine at Harvard Medical School provides an ideal setting for training outstanding junior scientists committed to reducing the burden of infectious diseases, because of the Department's multi-disciplinary work in the control of tuberculosis and HIV in international sites. In conjunction with the foreign site in Peru and with the Departments of Epidemiology and Biostatistics at the Harvard School of Public Health, as well as the Division of Social Medicine and Health Inequalities at the Brigham and Women's Hospital, this environment will maximize Dr. Mitnick's potential to pursue an independent research career as a chronic, infectious-disease epidemiologist. [unreadable] [unreadable] [unreadable] [unreadable]